Poor Response to Bevacizumab Correlates With Higher IL-6 and IL-8 Aqueous Cytokines in AMD.

Purpose: To evaluate the effect of intravitreal bevacizumab on aqueous levels of a panel of 12 inflammatory cytokines in patients with neovascular age-related macular degeneration (nAMD) and correlate response to treatment, as measured by change in the central subfovea thickness (CST), with cytokine levels. Methods: Thirty-three treatment-naïve patients with nAMD received a loading dose of intravitreal bevacizumab consisting of three injections at six weekly intervals. The aqueous samples prior to the first (baseline), second (week 6), and third (week 12) injections were analyzed for cytokine levels. Participants were subgrouped based on changes in CST on spectral-domain optical coherence tomography (SD-OCT) at 12 weeks. Group 1 included patients with a decrease in CST (responders; n = 27). Group 2 included patients who had no decrease in CST (poor responders; n = 6). Results: Aqueous IL-8 was the only cytokine to demonstrate a significant difference in levels between responders and poor responders, with higher interleukin-8 (IL-8) at week 12 in the poor responder group. Aqueous IL-6 and IL-8 levels showed a positive correlation with CST on SD-OCT (Spearman r = 0.45 and 0.55, respectively). There was a temporal increase overall in cytokine concentration accompanying bevacizumab treatment. Conclusions: Aqueous IL-6 and IL-8 may be important markers of treatment response or poor response in nAMD. Future therapeutic strategies may include targeted treatment against both vascular endothelial cell growth factor (VEGF) and IL-6 and/or IL-8 in patients who do not respond to anti-VEGF treatment alone.

Multimodal Analysis of the Retinal Manifestations of Tuberous Sclerosis Complex: A Case Series.

BACKGROUND AND OBJECTIVE: We used a multi-modal imaging approach including fundus fluorescein angiography (FFA) to assess the retinal lesions in tuberous sclerosis complex (TSC) and evaluate their correlation with intracranial tuber burden on magnetic resonance imaging (MRI). PATIENTS AND METHODS: Participants with TSC underwent bilateral fundus photography, optical coherence tomography (OCT), infrared (IR) imaging, and FFA. Participants' most recent MRI brain scans were analyzed to determine intracranial tuber load. RESULTS: Nine participants were included. OCT identified all retinal astrocytic hamartoma (RAH) lesions, IR identified 75%, fundus photography identified 63%, and FFA detected just 57%. On FFA, 20% of flat-type hamartomas and all multi-nodular and transitional types were hyperfluorescent. There were significant positive correlations between the quantities of intracranial tubers and all TSC-retinal lesions (r = 0.8, P < 0.01) and all RAH lesions (r = 0.8, P = 0.01). CONCLUSIONS: A multimodal imaging-based approach with fundal photography, IR imaging, and OCT should be used to assess the retina in TSC as it may indicate the intracranial tuber burden. [Ophthalmic Surg Lasers Imaging Retina 2024;55:568-574.].

Cardiovascular Autonomic Function and Progression of Age-Related Macular Degeneration in The Irish Longitudinal Study of Ageing (TILDA).

Purpose: To examine if changes in hemodynamic measures during an orthostatic challenge were associated with progression of age-related macular degeneration (AMD) over a 4-year period in The Irish Longitudinal Study on Ageing. Methods: Participants with AMD who underwent an active stand (AS) test at wave 1 (2009/2010) and retinal photographs at both wave 1 and wave 3 (2014/2015) were included (N = 159: 121 with no AMD progression and 38 with progression). Beat-to-beat hemodynamic data were non-invasively collected using a Finometer MIDI device during the AS at wave 1, recording systolic blood pressure (sBP), diastolic blood pressure (dBP), mean arterial pressure (MAP), and heart rate. Cardiac output, stroke volume, and total peripheral resistance (TPR) were derived from these measures. Baseline characteristics were compared between groups with and without AMD progression. Mixed-effects linear regression models were used to assess the association between changes in hemodynamic parameters during the AS and AMD progression, controlling for known AMD-associated risk factors. Results: At baseline, increasing age and lower dBP were significantly associated with AMD progression. Mixed-effects models for the period between standing and 10 seconds post-stand revealed significant associations with AMD progression with a steeper drop in dBP and a slower drop in TPR. Between 10 and 20 seconds post-stand, AMD progression was significantly associated with less pronounced reduction in heart rate. Conclusions: These observational data suggest that impaired hemodynamic responses within the first 20 seconds of orthostasis may be associated with the progression of AMD.

Evaluation of Inflammation in the Peripheral Multiple Sclerosis Retina Using Ultra-Widefield Optical Coherence Tomography: A Pilot Study.

BACKGROUND AND OBJECTIVE: Reports of fundus fluorescein angiography (FFA) in active multiple sclerosis (MS) have shown peripheral perivenous sheathing. We sought to assess the feasibility of ultra-widefield (UWF) FFA and optical coherence tomography (OCT) in assessing the peripheral retina in MS. MATERIALS AND METHODS: Participants with MS and healthy controls underwent bilateral UWF fundus photography and FFA. Swept-source OCTs were captured centrally, peripherally, and to delineate any abnormalities visualized. RESULTS: We recruited five people with relapsing remitting MS, with a mean age of 36.9 (± 9.9), mean disease duration of 11 years (± 6.3), and a median expanded disability status score of 0.75 (0 to 2.5). In all MS participants, the disease was not active clinically or radiologically. Using UWF-FFA and OCT, we did not detect clear evidence of peripheral retinal abnormalities, which is consistent with the participants having inactive MS. CONCLUSION: A pilot study using UWF-FFA and peripheral OCT to examine the retina in MS suggests that it may be useful to perform a larger prospective longitudinal study to establish its potential as a monitor of disease activity. [Ophthalmic Surg Lasers Imaging Retina 2023;54:586-588.].

Near-Complete Drusen Resolution With Brolucizumab: A Mechanism for Proinflammatory Mediated Drusen Clearance?

A 68-year-old woman with macular drusen was diagnosed with neovascular age-related macular degeneration (AMD) and treated with intravitreal brolucizumab. She had a good response to treatment with reduced height of the pigment epithelial detachment, and a good visual outcome. Remarkably, she had a near-complete resolution of macular drusen, yet this was accompanied by the development of anterior uveitis. We propose a proinflammatory-based mechanism for the brolucizumab-induced drusen resorption. Identifying the biochemical pathways responsible could hold the potential to discover novel forms of therapy for the treatment of AMD. [Ophthalmic Surg Lasers Imaging Retina 2023;54:371-374.].

Irish National Diabetic RetinaScreen Programme: report on five rounds of retinopathy screening and screen-positive referrals. (INDEAR study report no. 1).

OBJECTIVE: To study the uptake of annual diabetic retinopathy screening and study the 5-year trends in the detection of screen-positive diabetic retinopathy and non-diabetes-related eye disease in a cohort of annually screened individuals. DESIGN: Retrospective retinopathy screening attendance and retinopathy grading analysis. SETTING: Community-based retinopathy screening centres for the Diabetic RetinaScreen Programme. PARTICIPANTS: 171 557 were identified by the screening programme to be eligible for annual diabetic retinopathy screening. 120 048 individuals over the age of 12 consented to and attended at least one screening appointment between February 2013 to December 2018. MAIN OUTCOME MEASURES: Detection rate per 100 000 of any retinopathy, screen-positive referrable retinopathy and nondiabetic eye disease. RESULTS: Uptake of screening had reached 67.2% in the fifth round of screening. Detection rate of screen-positive retinopathy reduced from 13 229 to 4237 per 100 000 screened over five rounds. Detection of proliferative disease had reduced from 2898 to 713 per 100 000 screened. Non-diabetic eye disease detection and referral to treatment centres increased almost eightfold from 393 in round 1 to 3225 per 100 000 screened. The majority of individuals referred to treatment centres for ophthalmologist assessment are over the age of 50 years. CONCLUSIONS: Screening programme has seen a reduced detection rate both screen-positive retinopathy referral in Ireland over five rounds of screening. Management of nondiabetic eye diseases poses a significant challenge in improving visual outcomes of people living with diabetes in Ireland.

Decreased CSF1R Signaling and the Accumulation of Reticular Pseudo-Drusen?

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is caused by dominant-acting mutations in the gene colony-stimulating factor 1 receptor (CSF1R). It is an ultra-rare leukoencephalopathy that involves demyelination of white matter and early-onset dementia. It has been well validated that mutations in the kinase region of the gene cause decreased signaling of the receptor via its two cognate ligands interleukin-34 (IL-34) and colony-stimulating factor-1 (CSF-1). In this article, we report a thorough analysis of retinal integrity in a 48-year-old genetically diagnosed ALSP patient. We show that although the optic nerve, optic chiasm, and optic tracts are relatively preserved, the patient has visual field deficits likely due to optic radiation and/or cortical atrophy. Intriguingly, we report the appearance of inner retinal vascular leakage and the appearance of reticular pseudo-drusen (RPD)-like deposits. We propose that the early stages of RPD accumulation may be associated with an attenuated CSF-1 receptor signaling axis. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:666-671.].

Dysregulated claudin-5 cycling in the inner retina causes retinal pigment epithelial cell atrophy.

Age-related macular degeneration (AMD) is the leading cause of central retinal vision loss worldwide, with an estimated 1 in 10 people over the age of 55 showing early signs of the condition. There are currently no forms of therapy available for the end stage of dry AMD, geographic atrophy (GA). Here, we show that the inner blood-retina barrier (iBRB) is highly dynamic and may play a contributory role in GA development. We have discovered that the gene CLDN5, which encodes claudin-5, a tight junction protein abundantly expressed at the iBRB, is regulated by BMAL1 and the circadian clock. Persistent suppression of claudin-5 expression in mice exposed to a cholesterol-enriched diet induced striking retinal pigment epithelium (RPE) cell atrophy, and persistent targeted suppression of claudin-5 in the macular region of nonhuman primates induced RPE cell atrophy. Moreover, fundus fluorescein angiography in human and nonhuman primate subjects showed increased retinal vascular permeability in the evening compared with the morning. These findings implicate an inner retina-derived component in the early pathophysiological changes observed in AMD, and we suggest that restoring the integrity of the iBRB may represent a novel therapeutic target for the prevention and treatment of GA secondary to dry AMD.

Prevalence of age-related macular degeneration associated genetic risk factors and 4-year progression data in the Irish population.

BACKGROUND/AIMS: Age-related macular degeneration (AMD) is estimated to affect 196 million people >50 years old globally. Prevalence of AMD-associated genetic risk factors and rate of disease progression are unknown in Ireland. METHODS: Prevalence of AMD-associated genetic risk variants, complement factor H (CFH) rs1061170, age-related maculopathy susceptibility 2 (ARMS2) rs10490924, component 3 (C3) rs2230199, complement factor B (CFB) rs641153 and superkiller viralicidic activity 2-like (SKIV2L) rs429608 and 4-year progression data in a population-representative cohort (The Irish Longitudinal study on Ageing (TILDA)) were assessed. 4473 participants ≥50 years were assessed. 4173 had no disease n=1843; 44% male and n=2330; 56% female, mean age 60±9.0, 300 had AMD n=136; 45% male and n=164; 55% female, mean age 64±9.0. A 4-year follow-up was undertaken with 66% of AMD cases attending. Progression and regression from early to late AMD were measured. Genetic association as indicators of disease and as predictors of progression were assessed by multinomial logistic regression. RESULTS: Older age and the presence of CFH and ARMS2 risk alleles are two main risk factors associated with the prevalence of AMD in the TILDA cohort. 23% progressed to a higher grade of AMD. Carriers of CFH risk allele showed a strong association for disease progression. Heterozygosity for ARMS2 risk allele predicted progression to late AMD. 75% of those who progressed from early to late disease had soft drusen and hyperpigmentation at baseline. CONCLUSIONS: The prevalence of risk-associated genes and 4-year progression rates of AMD in this Ireland cohort are comparable with other Caucasian populations. CFH Y402H is associated with disease progression, with soft drusen and hyperpigmentation as high-risk features.

Homocysteine, methylenetetrahydrofolate reductase C677T polymorphism, and risk of retinal vein occlusion: a meta-analysis.

OBJECTIVE: To assess the role of plasma total homocysteine (tHcy) concentrations and homozygosity for the thermolabile variant of the methylenetetrahydrofolate reductase (MTHFR) C677T gene as risk factors for retinal vascular occlusive disease. DESIGN: Retinal vein occlusion (RVO) is an important cause of vision loss. Early meta-analyses showed that tHcy was associated with an increased risk of RVO, but a significant number of new studies have been published. PARTICIPANTS AND/OR CONTROLS: RVO patients and controls. METHODS: Data sources included MEDLINE, Web of Science, and PubMed searches and searching reference lists of relevant articles and reviews. Reviewers searched the databases, selected the studies, and then extracted data. Results were pooled quantitatively using meta-analytic methods. MAIN OUTCOME MEASURES: tHcy concentrations and MTHFR genotype. RESULTS: There were 25 case-control studies for tHcy (1533 cases and 1708 controls) and 18 case-control studies for MTHFR (1082 cases and 4706 controls). The mean tHcy was on average 2.8 micromol/L (95% confidence interval [CI], 1.8-3.7) greater in the RVO cases compared with controls, but there was evidence of between-study heterogeneity (P<0.001, I(2) = 93%). There was funnel plot asymmetry suggesting publication bias. There was no evidence of association between homozygosity for the MTHFR C677T genotype and RVO (odds ratio [OR] 1.20; 95% CI, 0.84-1.71), but again marked heterogeneity (P = 0.004, I(2) = 53%) was observed. CONCLUSIONS: There was some evidence that elevated tHcy was associated with RVO, but not homozygosity for the MTHFR C677T genotype. Both analyses should be interpreted cautiously because of marked heterogeneity between the study estimates and possible effect of publication bias on the tHcy findings. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Long-term outcomes after laparoscopic antireflux surgery.

OBJECTIVES: We studied the long-term outcomes of laparoscopic antireflux surgery (LARS) and the factors that determine it, as neither has been previously well established. METHODS: From September 1993 (start of our program) to September 1999, 441 patients underwent LARS. Preoperative symptoms and the results of esophageal functional studies as well as details of the operation and follow-up were recorded prospectively in our database. In 2004, with the help of a private investigator, we were able to contact 288 (65%). There were no differences in presentation profiles of those patients contacted and those we could not. RESULTS: At a median follow-up of 69 months, individual symptoms, among those who had it preoperatively, were as follows: heartburn (N = 282) improved in 254 (90%) and resolved in 188 (67%); regurgitation (N = 258) improved in 238 (92%) and resolved 199 (70%); dysphagia (N = 123) improved in 96 (78%) and resolved in 76 (62%); cough (N = 119) improved in 82 (69%) and resolved in 48 (40%); and hoarseness (N = 106) improved in 73 (69%) and resolved in 50 (47%). Univariate regression analysis showed that the presence of heartburn (P= 0.02), male gender (P= 0.03), and younger age (P= 0.04) predicted symptom resolution, whereas preoperative dysphagia (P= 0.03), airway manifestations (P= 0.03), bloating (P= 0.04), and defective esophageal motility (P= 0.08) were negative predictive factors. By multivariate analysis, male gender, dysphagia, and age remained significant (P < 0.05). Seven patients (2%) developed a new onset of dysphagia; 32 patients (11%) developed new or increased diarrhea and 27 patients (9%) developed bloating postoperatively. One hundred nineteen patients (41%) were taking some form of antacid medication; 66 (23%) patients were using PPIs and 10 (3%) had undergone reoperation. CONCLUSION: LARS provides effective long-term relief of GERD. Younger patients, men, and those without dysphagia are predictors of superior outcomes.

Hepatocyte growth factor induces retinal vascular permeability via MAP-kinase and PI-3 kinase without altering retinal hemodynamics.

PURPOSE: Although vascular endothelial growth factor (VEGF) is a key mediator of retinal vascular permeability (RVP), there may be additional humoral contributors. Hepatocyte growth factor (HGF) induces endothelial cell separation, regulates expression of cell adhesion molecules and is increased in the vitreous fluid of patients with proliferative diabetic retinopathy. The purpose of this study was to evaluate the in vivo effects of HGF on RVP and retinal hemodynamics and delineate the signaling pathways. METHODS: RVP was assessed by vitreous fluorescein fluorophotometry in rats. Time course and dose-response were determined after intravitreal HGF injection. MAP kinase (MAPK), phosphatidylinositol 3-kinase (PI-3 kinase), and protein kinase C (PKC) involvement were examined by using selective inhibitors. Retinal blood flow (RBF) and mean circulation time (MCT) were evaluated by video fluorescein angiography. RESULTS: HGF increased RVP in a time- and dose-dependent manner. HGF-induced RVP was evident 5 minutes after injection, and reached maximal levels after 25 minutes (+107% versus vehicle, P=0.002). This effect was comparable to that of maximum VEGF stimulation (134%+/-128% at 25 ng/mL). Selective inhibitors of MAPK (PD98059) and PI-3 kinase (LY294002) suppressed HGF-induced RVP by 86%+/-44% (P=0.015) and 97%+/-59% (P=0.021), respectively. Non-isoform-selective inhibition of PKC did not significantly decrease HGF-induced RVP. Although VEGF increases RBF and reduces MCT, HGF did not affect either. CONCLUSIONS: HGF increases RVP in a time- and dose-dependent manner at physiologically relevant concentrations with a magnitude and profile similar to that of VEGF, without affecting retinal hemodynamics. Thus, HGF may represent another clinically significant contributor to retinal edema distinct from the actions of VEGF.

Recurrence of retinal pigment epithelial changes after macular translocation with 360 degrees peripheral retinectomy for geographic atrophy.

OBJECTIVE: To assess the prevalence of recurrence of macular geographic atrophy (GA) of the retinal pigment epithelium (RPE) after macular translocation with 360 degrees retinectomy (MT360) in one institution. METHODS: A retrospective review of all cases of GA that were treated with MT360 in 1 institution. Demographic and clinical data including the duration of preoperative visual loss, preoperative and postoperative visual acuity, and the prevalence of postoperative foveal RPE atrophy were recorded for these patients, and these data were compared with similar data from patients who underwent MT360 for neovascular age-related macular degeneration (AMD) as part of the prospective Duke Macular Translocation Study, Duke University Eye Center, Durham, NC. RESULTS: Four eyes in 4 patients with GA secondary to AMD underwent MT360 and were compared with 63 eyes in 63 patients who underwent MT360 for neovascular AMD as part of the Duke Macular Translocation Study. The mean duration of preoperative visual loss was higher in the GA group (11.3 months) than in the neovascular AMD group (1.7 months) (P = .08). The prevalence of postoperative foveal RPE atrophy was significantly higher in the GA group (n = 3; 75.0%) than in the neovascular AMD group (n = 5; 8.3%) (P<.01); in the GA group, this corresponded to recurrence of the GA lesions. In contrast, the postoperative RPE atrophy seen in the neovascular AMD group was due to postoperative mechanical forces such as laser therapy or RPE tearing. There was no significant difference in the mean preoperative or postoperative visual acuity in either group. CONCLUSIONS: Subfoveal RPE atrophy can reoccur following MT360 in eyes with nonneovascular AMD and GA; RPE atrophy similar to this has not been found in a large consecutive series of patients with neovascular AMD after MT360. Further research is needed to assess if the potential for visual recovery in eyes with end-stage nonneovascular AMD is outweighed by the possibility of postoperative recurrence of GA.

Vision-related quality of life in patients with bilateral severe age-related macular degeneration.

PURPOSE: To determine the quality of life (QOL) of patients with bilateral severe age-related macular degeneration (AMD) before macular translocation with 360 degrees peripheral retinectomy. DESIGN: Prospective, consecutive, noncomparative case series. METHODS: An observational study assessed vision-related and general health QOL using the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) and the Medical Outcomes Study 12-item short form (SF-12) surveys, respectively. Mean QOL scores were correlated with patient age, duration of vision loss, and visual function. Mean QOL scores in study patients were compared with mean QOL scores in groups of patients with low vision, patients with AMD of varying severity, and reference populations. MAIN OUTCOME MEASURES: National Eye Institute VFQ-25 and SF-12 QOL scores. RESULTS: Seventy patients with a mean age of 76.4 years were studied. Mean distance visual acuity (VA) was 62.4 (Early Treatment Diabetic Retinopathy Study letters), mean near VA was 0.81 (logarithm of the minimum angle of resolution), and mean reading speed was 74.9 words per minute. Important NEI VFQ-25 quality of vision subscales (general vision, difficulty with distance tasks, difficulty with near tasks) and vision-specific subscales (dependency, role difficulties, mental health, social function limitations) tended to correlate negatively with increasing patient age and duration of vision loss, but correlated positively with better VA and reading speed. The mean QOL scores for these important quality of vision and vision-specific subscales were significantly worse than or similar to mean scores in patients with low vision, and significantly worse than scores in patients with AMD of varying severity and a reference population. The mean SF-12 physical composite score in study patients was similar to that seen in patients with AMD of varying severity, but significantly higher than that in patients with low vision and a reference population. The SF-12 mental composite score in study patients was similar to those of all 3 comparison groups. CONCLUSIONS: Patients with bilateral severe AMD have vision-related QOL similar to that of patients with low vision but significantly worse than those of patients with AMD of varying severity and persons without eye disease. This inability to perform vision-related daily tasks is not related to general health problems.

Quality of life after macular translocation with 360 degrees peripheral retinectomy for age-related macular degeneration.

PURPOSE: To determine patients' quality of life (QOL) after macular translocation with 360 degrees peripheral retinectomy (MT360) for age-related macular degeneration. DESIGN: Prospective, interventional, consecutive, noncomparative case series. METHODS: A prospective study assessed QOL 1 year after MT360 and its relation to postoperative visual function. The 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) and the Medical Outcomes Study 12-item short form (SF-12) health survey were used to assess vision-related QOL and general health, respectively. Surveys were administered preoperatively and postoperatively. Postoperative NEI VFQ-25 QOL and SF-12 subscale scores for all patients were compared with the preoperative scores. Preoperative and postoperative distance and near visual acuities (VAs) and reading speed were assessed. Changes in NEI VFQ-25 QOL subscale scores were compared in patients with and without improved visual function. Postoperative NEI VFQ-25 QOL subscale scores in patients with distance VA of >or=69 Early Treatment Diabetic Retinopathy Study letters, near VA of >or=20/70, and reading speed of >or=90 words per minute were compared with subscale scores in patients with worse postoperative visual function. MAIN OUTCOME MEASURES: National Eye Institute VFQ-25 and SF-12 QOL scores and their association with distance VA, near VA, and reading speed. RESULTS: In total, 50 patients with a mean age of 76.9 years were studied. Postoperative mean NEI VFQ-25 QOL scores were higher than the preoperative mean scores, and this difference was significant for important vision-specific subscales. Patients with improved visual function had greater mean changes in NEI VFQ-25 QOL scores than those with no improvement. Patients with the outlined higher levels of visual function had greater mean NEI VFQ-25 QOL scores than those who had worse visual function. Preoperative and postoperative mean SF-12 QOL scores were similar. CONCLUSIONS: Macular translocation with 360 degrees peripheral retinectomy was associated with improvement in vision-related QOL. The amount of improvement was greatest in patients with postoperative improvement in visual function, and the best postoperative vision-related QOL was seen in patients with better postoperative visual function. This was not associated with a change in patients' general health.

Meta-analysis of plasma homocysteine, serum folate, serum vitamin B(12), and thermolabile MTHFR genotype as risk factors for retinal vascular occlusive disease.

PURPOSE: To assess the role of plasma total homocysteine (tHcy) levels, serum folate and vitamin B(12)levels, and homozygosity for the thermolabile methylenetetrahydrofolate reductase genotype (TT) as risk factors for retinal vascular occlusive disease. DESIGN: Meta-analysis of literature. METHODS: A MEDLINE search was performed to identify all published case-control studies of plasma tHcy levels, serum folate and vitamin B(12) levels, and TT genotype in persons with retinal vascular occlusive disease. Main outcome measures included calculation of plasma tHcy, serum folate, and serum vitamin B(12) standard differences and odds ratios (OR) of TT genotype between cases and controls. RESULTS: In total, 614 patients with all types of retinal vein occlusion had higher plasma tHcy levels than 762 control subjects (standard difference, 0.867; 95% confidence interval [CI] = 0.735, 0.999; P <.001). Plasma tHcy levels were also higher in 154 patients with retinal artery occlusion compared with 358 control subjects (standard difference 1.174; 95% CI = 0.947, 1.402; P <.001). Serum folates, but not vitamin B(12) levels, were lower in 287 patients with retinal vascular occlusion than in the same number of control subjects (standard difference, 0.508; 95% CI = 0.340, 0.675; P <.001; and -0.060; 95% CI = -0.024, 0.104; P =.474, respectively). Similar proportions of 690 patients with retinal vein occlusion and 2754 control subjects demonstrated the TT genotype (OR = 1.332; 95% CI = 0.995, 1.783; P =.054) as did 152 patients with retinal artery occlusions and 435 control subjects (OR = 1.716; 95% CI = 0.977, 3.014; P =.060). CONCLUSIONS: Retinal vascular occlusion is associated with elevated plasma tHcy levels and low serum folate levels, but not serum vitamin B(12) levels and TT genotype. Until a prospective multicenter trial is undertaken, plasma tHcy levels and serum folate levels should be determined in patients with retinal vascular occlusions, and dietary supplementation with low doses of folate and vitamin B(12) should be considered for affected persons.

Characterization of changes in blood vessel width and tortuosity in retinopathy of prematurity using image analysis.

Many retinal diseases are characterised by changes to retinal vessels. For example, a common condition associated with retinopathy of prematurity (ROP) is so-called plus disease, characterised by increased vascular dilation and tortuosity. This paper presents a general technique for segmenting out vascular structures in retinal images, and characterising the segmented blood vessels. The segmentation technique consists of several steps. Morphological preprocessing is used to emphasise linear structures such as vessels. A second derivative operator is used to further emphasise thin vascular structures, and is followed by a final morphological filtering stage. Thresholding of this image is used to provide a segmented vascular mask. Skeletonisation of this mask allows identification of points in the image where vessels cross (bifurcations and crossing points) and allows the width and tortuosity of vessel segments to be calculated. The accuracy of the segmentation stage is quite dependent on the parameters used, particularly at the thresholding stage. However, reliable measurements of vessel width and tortuosity were shown using test images. Using these tools, a set of images drawn from 23 subjects being screened for the presence of threshold ROP disease is considered. Of these subjects, 11 subsequently required treatment for ROP, 9 had no evidence of ROP, and 3 had spontaneously regressed ROP. The average vessel width and tortuosity for the treated subjects was 96.8 microm and 1.125. The corresponding figures for the non-treated cohort were 86.4 microm and 1.097. These differences were statistically significant at the 99% and 95% significance level, respectively. Subjects who progressed to threshold disease during the course of screening showed an average increase in vessel width of 9.6 microm and in tortuosity of +0.008. Only the change in width was statistically significant. Applying a simple retrospective screening paradigm based solely on vessel width and tortuosity yields a screening test with a sensitivity and specificity of 82% and 75%. Factors confounding a more accurate test include poor image quality, inaccuracies in vessel segmentation, inaccuracies in measurement of vessel width and tortuosity, and limitations inherent in screening based solely on examination of the posterior pole.

Rapid and durable recovery of visual function in a patient with von hippel-lindau syndrome after systemic therapy with vascular endothelial growth factor receptor inhibitor su5416.

PURPOSE: To present a case of rapid and durable recovery of visual function in a patient with von Hippel-Lindau syndrome and optic nerve head hemangioblastoma after systemic treatment with the vascular endothelial growth factor (VEGF) receptor inhibitor SU5416. DESIGN: Interventional case report. METHODS: Visual function parameters, including visual acuity, automated visual field, and contrast sensitivity, were evaluated using standardized methods repeatedly over a 15-month period. Fundus photographs and fluorescein angiograms were also obtained. Central nervous system lesions were monitored by computed tomography (CT) and magnetic resonance imaging (MRI) scans. Treatment involved the systemic administration of the VEGF receptor inhibitor SU5416. MAIN OUTCOME MEASURES: Clinical presentation, visual acuity using Early Treatment Diabetic Retinopathy Study protocol, Humphrey automated perimetry, (Zeiss Humphrey Systems, Dublin, CA) Vistech contrast sensitivity (Vistech Consultants Inc., Dayton, OH) Farnsworth (Farnsworth-Munsell Color Services, New Windsor, NY) dichotomous panel D-15, retinal photography, fluorescein angiography, and CT and MRI scans. RESULTS: Within 4 weeks of therapy, visual acuity had improved from 20/32(-2) to 20/16(-1), the visual field had expanded from being circumferentially constricted to within 8 degrees of fixation to normal, and contrast sensitivity improved in all but the lowest spatial frequency (1.5 cycles/degree). No change was observed in lesion size by fundus photography. Improvement has been maintained over 18 months with intermittent SU5416 therapy. CONCLUSIONS: We report rapid, extensive, and durable recovery of visual function after systemic administration of the VEGF receptor inhibitor SU5416 to a patient with VHL syndrome and optic nerve head hemangioblastoma. These findings suggest that continued evaluation of VEGF inhibitors for ocular neovascular disorders is warranted.